Scandinavian journal of urology and nephrology. Supplementum最新文献

Tobacco smoking is the main known cause of urinary bladder cancer in humans. In most populations, over half of cases in men and a sizeable proportion in women are attributable to this habit. Epidemiological studies conducted in different populations have shown a linear relationship between intensity and duration of smoking and risk. Quitting smoking reduces the risk of bladder cancer. Smoking black (air-cured) cigarettes results in a higher risk than smoking blond (flue-cured) tobacco cigarettes; results on inhalation patterns and use of filter are not consistent. Cigar and pipe smoking also increases the risk of bladder cancer; data on other tobacco products are limited. The evidence for non-transitional bladder carcinoma is limited, but consistent with an increased risk. The available evidence does not point towards a different carcinogenic effect of tobacco smoking in men and women or in whites and blacks. Data on involuntary smoke and use of smokeless tobacco products are limited, but do not suggest an increased risk of bladder cancer.

A few data sets have been used for assessing the risk of radiation-associated bladder cancer. The most important are the Japanese atomic bomb survivors and patients exposed to ionizing radiation for medical purposes. According to a report from the United Nations Commission on the Effect of Ionizing Radiation, there is convincing evidence of a relationship between exposure to ionizing radiation and bladder cancer. In contrast to many other malignancies it is not clear how age at exposure and gender affect the risk of bladder cancer. Furthermore, the potential interaction between smoking and radiation exposure needs to be studied in greater detail.

Bladder cancer is an increasingly important international public health problem. As a multifactorial disease, both environmental and genetic factors are involved in its development and progression. This neoplasm is a paradigm for the participation of low-penetrance genetic variants (GSTM1-null and NAT2-slow) and provides the best established gene-environment interaction in cancer (NAT2-slow * tobacco). Genetic variants in nucleotide excision and double strand break DNA repair pathways have provided promising results, ERCC2-XPD rs238406 being the most consistent variant associated with an increased of bladder cancer risk, by itself and by interacting with tobacco. Variants in other pathways such as cell-cycle control, 1-C metabolism and inflammation have been studied, although the results are inconsistent. Three very large whole genome association studies are being undertaken using the same genotyping platform. Their results will be available soon. Genetic variants have seldom been considered as markers of prognosis or response to therapy in this tumour. The results of these studies are inconclusive. Other issues that need to be addressed are the role of genetic variants in different population subgroups--defined by ethnicity, gender and age, among others--and the association with bladder cancer subphenotypes according to clinical, pathological and molecular characteristics of the tumour. This endeavour can only be achieved by integrating multidisciplinary tools and information. Can this information be applied better to identify high-risk populations? Can the information be used to better assess prognosis or predict response to therapy? These questions require large, well-designed, multicentre studies to be conducted. Funding agencies should be aware of these needs.

This study assessed the epidemiology of bladder cancer in Russia. The available publications in Russian were analysed, as well as information from the database of N. N. Blokhin Cancer Research Center, accumulating non-uniform data from different cities and regions of Russia. In 2006 there were 68 129 patients with bladder cancer in Russia, accounting for 2.8% of all cancer cases, with unknown proportions of males and females. In the same year 11 973 new bladder cancer cases were diagnosed, with morphological confirmation in 82.3% of cases. From 1999 to 2004 the incidence of bladder carcinoma increased by 5.3% in males and by 12.5% in females. In 2006 57.4% of patients with newly diagnosed disease were staged as T1 and T2, 26.8% as T3 and 11.4% as T4 bladder cancer cases. The mortality rate of patients with bladder carcinoma increased by 10.9% in males from 1999 to 2004 and did not change in females. In conclusion, over the past 10 years both the prevalence and incidence of bladder carcinoma have increased in Russia. There was a trend towards detecting less advanced cases of the disease, and stages T3 and T4 are diagnosed less frequently today than in 1996. As a result the mortality rate of bladder cancer patients within the first year from diagnosis has decreased, although the overall mortality rate in males has risen.

Statistics on the incidence of bladder cancer are particularly hard to interpret, because of changing classification, variations in counting of multiple cancers in the same individual and, most importantly, the variable inclusion of non-invasive cancers in different data sets. Mortality statistics are almost certainly more comparable, but as indirect estimators of disease risk, require some cautious interpretation, because of differing survival between populations, and over time. Cancer of the bladder is estimated to be the ninth most common cause of cancer worldwide (357 000 cases in 2002) and the 13th most numerous cause of death from cancer (145 000 deaths). Rates in males are three to four times those in females. Incidence rates are high in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. The highest estimated mortality is in Egypt, where rates are more than three times greater than the highest rates in Europe and eight times those in the USA. In the USA, the incidence in whites is higher than in blacks. In general, in Western countries, incidence rates have been rising, but the increase has slowed or stopped in many. Mortality rates are, for the most part, decreasing. Trends are more variable in developing countries. To some extent, the geography and time trends are related to prevalence of known risk factors, especially exposure to tobacco (responsible for almost one-third of bladder cancer deaths) and, in some specific areas, schistosomiasis.

First degree relatives of patients with bladder cancer have a two-fold increased risk of bladder cancer but high-risk bladder cancer families are extremely rare. There is no clear Mendelian inheritance pattern that can explain the increased familial risk. This makes classical linkage studies for the mapping of susceptibility genes impossible. The disease is probably caused by a combination of exposure to exogenous carcinogens and a large number of susceptibility genes with modest effects. Genome-wide association studies are better suited to identify these genes. Three such studies are currently underway and are expected to report their results in 2008.

The introduction of tissue microarray (TMA) methodology 10 years ago has provided a valuable tool for high-throughput genomic and proteomic analyses. Using this method hundreds of minute tissue samples can be investigated on one microscopic glass slide. Several studies demonstrated that these small tissue areas are representative for the entire tumour block and can provide reliable information on the relation of molecular markers and clinical outcome of the patient. Types of TMA used in bladder cancer research include defined clinical case series, stage-specific series (e.g. pT1), stage progression series, TMAs containing all specimens from clinical trials for specific therapies, flat (pre)neoplastic lesions, cell culture pellets and mouse model TMAs. The TMA technique has frequently been used in bladder cancer research to evaluate immunohistochemical candidate markers for prognosis and to reveal the amplification frequency of candidate oncogenes in regions with copy number alterations detected by comparative genomic hybridization and array-based methods. In addition, multimarker expression studies of several specific biological functions (e.g. apoptosis or cell-cycle proteins) or signal transduction pathways have been performed. TMAs are also used for validation of array-based gene expression studies on the protein level. TMA technology represents a crucial technique for translating new information on molecular changes in bladder cancer into clinical practice.